International Journal of Medical Sciences

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12 December 2017

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Int J Med Sci 2017; 14(9):902-910. doi:10.7150/ijms.19965

Research Paper

Effect of YAP Inhibition on Human Leukemia HL-60 Cells

Min Chen1,2, Jian Wang2, Shi-Fei Yao1,2, Yi Zhao1,2, Lu Liu2, Lian-Wen Li1,2, Ting Xu1,2, Liu-Gen Gan1,2, Chun-Lan Xiao1,2, Zhi-Ling Shan2, Liang Zhong2✉, Bei-Zhong Liu1,2✉

1. Central Laboratory of Yong-chuan Hospital, Chongqing Medical University, Chongqing, 402160, China
2. Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China

Abstract

Background: Yes-associated protein (YAP), the nuclear effector of the Hippo pathway, is a candidate oncoprotein and participates in the progression of various malignancies. However, few reports have examined the effect of YAP inhibition in human leukemia HL-60 cells.

Methods: We examined the effects of YAP knockdown or inhibition using short hairpin RNA (shRNA) or verteporfin (VP), respectively. Western blot assays were used to determine the expression levels of YAP, Survivin, cyclinD1, PARP, Bcl-2, and Bax. Cell proliferation was assessed using the cell counting kit (CCK-8) assay. Cell cycle progression and apoptosis were evaluated by flow cytometry, and apoptotic cell morphology was observed by Hoechst 33342 staining.

Results: Knockdown or inhibition of YAP led to cell cycle arrest at the G0/G1 phase and increased apoptosis, inhibited cell proliferation, increased levels of Bax and cleaved PARP, and decreased levels of PARP, Bcl-2, Survivin, and cyclinD1. Moreover, Hoechst 33342 staining revealed increased cell nuclear fragmentation.

Conclusion: Collectively, these results show that inhibition of YAP inhibits proliferation and induces apoptosis in HL-60 cells. Therefore, a novel treatment regime involving genetic or pharmacological inhibition of YAP could be established for acute promyelocytic leukemia.

Keywords: Yes-associated protein, human leukemia HL-60 cells, shRNA, verteporfin, proliferation, apoptosis

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How to cite this article:
Chen M, Wang J, Yao SF, Zhao Y, Liu L, Li LW, Xu T, Gan LG, Xiao CL, Shan ZL, Zhong L, Liu BZ. Effect of YAP Inhibition on Human Leukemia HL-60 Cells. Int J Med Sci 2017; 14(9):902-910. doi:10.7150/ijms.19965. Available from http://www.medsci.org/v14p0902.htm